Chemistry Commons^™

Synthesis And Evaluation Of 4-Cycloheptylphenols As Selective Estrogen Receptor-Β Agonists (Serbas), K. L. Iresha Sampathi Perera, Alicia M. Hanson, Sergey V. Lindeman, Andrea Imhoff, Xingyun Lu, Daniel S. Sem, William A. Donaldson

Chemistry Faculty Research and Publications

A short and efficient route to 4-(4-hydroxyphenyl)cycloheptanemethanol was developed, which resulted in the preparation of a mixture of 4 stereoisomers. The stereoisomers were separated by preparative HPLC, and two of the stereoisomers identified by X-ray crystallography. The stereoisomers, as well as a small family of 4-cycloheptylphenol derivatives, were evaluated as estrogen receptor-beta agonists. The lead compound, 4-(4-hydroxyphenyl)cycloheptanemethanol was selective for activating ER relative to seven other nuclear hormone receptors, with 300-fold selectivity for the β over α isoform and with EC₅₀ of 30–50 nM in cell-based and direct binding assays.